Background: The use of bridge-enhanced anterior cruciate ligament (ACL) restoration (BEAR) procedures is on the rise. Yet, there is a paucity of literature describing the radiographic appearance of the ACL after this procedure. Purpose: To present the quantitative and qualitative postoperative changes in healing ACLs within the first 24 months after an ACL restoration procedure. Study Design: Case series; Level of evidence, 4. Methods: A total of 64 patients (64 knees, 19.4 ± 5 years, 57% women) underwent magnetic resonance imaging (MRI) of the knee 6, 12, and 24 months after ACL restoration surgery with an extracellular matrix scaffold as part of a randomized-controlled trial. The ACL sagittal elevation angle and tunnel positions, along with ACL volume, mean cross-sectional area (CSA), length, and normalized signal intensity (SI), were quantified from MRI. Patients were divided into quartiles based on SI at 24 months after surgery for inclusion in the qualitative analysis with an adapted framework for assessing tissue quality. Additional cases were selected for qualitative analysis based on clinical representations. Linear mixed modeling with Tukey post hoc corrections was used to analyze quantitative ACL healing parameters. Results: Tunnel positions were anatomic in 26.6% of femurs and 68.8% of tibias. The healing ACL sagittal elevation angle remained stable (<1° change between postoperative time points; P > .1) and was comparable with the contralateral native ACL (<2° difference between contralateral and BEAR at postoperative time points; P > .05) at all time points. The healing ACL volume and CSA decreased over time ( P < .01) but remained 20% (volume) and 15% (CSA) larger than the contralateral ACL at 24 months postoperatively (by 341 mm 3 volume and 6 mm 2 CSA; P < .001). The healing ACL length was constant over time (<1 mm change between postoperative time points; P > .1) and was 5% longer than the contralateral native ACL at final follow-up (by 1.8 mm; P = .027). The ACL SI decreased over time ( P < .001) and was 10% less than the contralateral ACL at 24 months (by 0.1 ± 0.3; P = .022). Seven relevant clinical scenarios were highlighted to show a spectrum of healing trajectories after ACL restoration surgery. Conclusion: The present study demonstrates that throughout 2 years of serial imaging after an ACL restoration procedure, the healing ACL becomes smaller cross-sectionally and more organized (lower normalized SI). Despite changes in the ACL size and ACL SI, the sagittal orientation remains unchanged and comparable with the contralateral native ACL. In the qualitative analysis, 7 distinct healing trajectories were identified. These data are important for interpreting postoperative imaging after the BEAR procedure, and for identifying that several healing trajectories exist after a restoration procedure. Further studies are warranted to identify patient-specific factors that may influence these trajectories. Registration: NCT02664545 (ClinicalTrials.gov identifier).

Sex-based differences in the meniscus have been examined, however, detailed location-specific meniscal size and MR-derived structural properties across meniscal regions are not well established. The proposed advanced imaging method allows for localized measurements of meniscus cross-sectional area (CSA) and signal intensity (SI) along the meniscal arc length in females and males. We hypothesized that females would exhibit smaller CSA values than males, when normalized to knee size, and that SI profiles would not differ between sexes. MR images of non-injured knees from 105 individuals (60 females; age 13-35 years) were analyzed to quantify CSA and SI along the medial and lateral meniscal arc lengths. Measurements were normalized to knee size to enable sex-based comparisons. Normalized lateral meniscus CSA did not differ significantly between females and males. In the medial meniscus, normalized anterior CSA was significantly smaller in females than males (0.04 mm2/mm; p < .001). No significant sex-based differences were observed in SI profiles along the arc length for either meniscus. This study demonstrates regional sex-based differences in normalized medial meniscus CSA but no differences in normalized SI for either meniscus. Given that differences of the normalized CSA were observed only in the anterior region of the medial meniscus, sex-based variations are not globally distributed across the meniscus but instead are confined to specific anatomical regions. This point underscores the importance of subregional analyses, as whole-structure analyses may exclude localized differences.

Background: Knee stability can be conferred passively by ligaments and menisci and actively by the neuromuscular system. We sought to determine the relationship between passive tibiofemoral alignment and dynamic constraint in patients undergoing anterior cruciate ligament (ACL) reconstruction (ACLR) and matched control participants who have been followed for more than a decade. Purpose/Hypothesis: It was hypothesized that (1) anterior tibial position would be greater in the surgical knee compared to the contralateral knee and when compared to knees of control participants, and (2) the surgical limb differences would be greater in the dynamic state during a 1-leg hop-for-distance landing task. Study Design: Controlled laboratory study. Methods: A total of 21 participants were recruited from a recently completed longitudinal clinical trial (NCT00434837): 10 patients who had undergone ACLR 10 to 15 years earlier and 11 matched control participants without knee injury. The 3-dimensional (3D) tibiofemoral position was extracted from each participant's computed tomography images as a measure of passive alignment. Dynamic 3D knee kinematics were recorded using biplane videoradiography during the landing of a 1-leg hop-for-distance activity. Side-to-side differences in knee kinematics between limbs were used as a measure of dynamic constraint. Peak anterior tibial position was the primary outcome measure, and peak anterior tibial position as a function of flexion angle was the secondary outcome measure. Results: The passive tibial position of patients with ACLR was 7.5 ± 2.3 mm more anterior compared to that of uninjured participants and 3.1 ± 1.1 mm more anterior than their contralateral limb ( P < .05). The mean peak dynamic anterior position was not different between surgical and contralateral limbs in ACLR patients ( P = .83). When anterior position was explored as a function of flexion angle, peak anterior tibial position was up to 10.3 mm greater in the ACLR surgical limbs ( P = .01) and 7.5 mm in the contralateral limbs ( P = .001) compared to the limbs of control participants. Conclusion: Passive alignment is abnormal long after ACLR, whereas side-to-side dynamic constraint is largely restored, but with a persistent bias toward greater anterior tibial position that is present bilaterally. Clinical Relevance: Compared with similar studies at earlier postoperative time points, the results at long-term follow-up suggest that ACL graft function deteriorates with time, which can be compensated for to some degree by the neuromuscular system.

BACKGROUND:Meniscal tears are frequently associated with anterior cruciate ligament (ACL) injuries. Evaluating longitudinal changes in meniscal integrity using quantitative magnetic resonance imaging after ACL surgery may provide valuable insight into joint recovery and subsequent reinjury risk. HYPOTHESES:(1) The cross-sectional area (CSA) and normalized signal intensity (SI) profiles of the lateral and medial menisci for the surgical knees would be greater than those of the contralateral uninjured knees observed at 6, 12, and 24 months after surgery. (2) The CSA and Constructive Interference in Steady State (CISS) SI profiles obtained at 24 months would be closer to those of the contralateral limb when compared with those of the 6- and 12-month time points. STUDY DESIGN:Cohort study; Level of evidence, 3. METHODS:Deidentified postsurgical CISS magnetic resonance imaging scans of patients (n = 82; median age 17.6 years; 42 females and 40 males; 57 ACL restoration and 25 ACL reconstruction) were analyzed. CSA and normalized CISS SI values were extracted from the lateral and medial menisci to create morphological profiles. Statistical parametric mapping was used to compare the CSA and normalized CISS SI profiles between the surgical and contralateral limbs to identify specific regions that were different among the menisci at 6, 12, and 24 months. RESULTS:The CSA and normalized CISS SI profiles of the anterior region of the medial menisci and lateral menisci for the surgical knees were greater than those of the contralateral uninjured knees, observed at 6, 12, and 24 months after surgery, whereas the posterior region CSA of the medial menisci was smaller. The lateral meniscus on the operated limb had a larger CSA and higher normalized CISS SI values than the lateral meniscus in the contralateral limb. The CSA and CISS SI profiles obtained at 24 months did not approach those of the contralateral limb. CONCLUSION:Significant changes occurred in both menisci after ACL surgery that did not return to baseline levels within 2 years. It is important to account for anatomic location when evaluating meniscal morphology in surgical knees and when evaluating the effects of ACL injuries on the surrounding tissues.

Purpose:The aim was to evaluate the associations between baseline variables on the development of a symptomatic knee and imaging evidence of posttraumatic osteoarthritis (PTOA) 15 years after anterior cruciate ligament (ACL) surgery. Methods:Data from 42 subjects enroled in the Tension Trial (NCT00434837) were evaluated at 15-year follow-up. Patient sex, meniscus injury, preoperative patient-reported outcomes (Knee Osteoarthritis Outcome Score [KOOS] function sports and recreation subscore [KOOS-sport], Short Form [SF]-36 mental health score), initial graft tension, and subsequent ACL surgery were evaluated to identify patients with a symptomatic knee using KOOS criteria (KOOS-Quality of life ≤87.5 and with at least two other subscores meeting the following thresholds (i.e., KOOS-Pain ≤86.1, KOOS-Symptoms ≤85.7, KOOS-Activities of daily living ≤86.8 and KOOS-Sport ≤85.0) and imaging evidence of PTOA (Osteoarthritis Research Society International [OARSI] radiographic score and Whole-Organ Magnetic Resonance Imaging Score [WORMS]) 15 years post-surgery using stepwise regression. Results:The presence of a baseline meniscus tear was associated with a seven-fold increase (p = 0.03) in odds for a symptomatic knee at 15 years. A higher preoperative KOOS-sport was associated with a decreased occurrence of a symptomatic knee (p = 0.06). A higher KOOS-sport and the presence of a meniscus tear at baseline were associated with a greater OARSI difference score (p = 0.03 and p = 0.05, respectively) 15 years after ACL reconstruction. The presence of the baseline meniscus tear was associated with a higher WORMS (p = 0.07) 15 years after ACL reconstruction. All other variables were not significant predictors, though loss to follow-up was over 50%. Conclusion:The presence of a minor meniscus injury was associated with a higher occurrence of a symptomatic knee and imaging evidence of posttraumatic osteoarthritis 15 years after ACL reconstruction. Furthermore, a higher preoperative KOOS-sport was associated with decreased occurrence of a symptomatic knee. Further studies are required to elucidate the associations of KOOS-sport with imaging PTOA. Level of Evidence:Level IV.

Background:The graft tension applied during anterior cruciate ligament (ACL) graft fixation (subsequently referred to as initial graft tension) could potentiate posttraumatic osteoarthritis (PTOA) and influence other outcomes. Purpose/Hypothesis:The purpose of this study was to analyze the effects of initial graft tension on imaging and patient-reported outcomes related to PTOA 15 years postreconstruction surgery. Clinical and functional outcomes were also assessed. It was hypothesized that (1) the high-tension group would have improved imaging findings and outcomes compared with the low-tension group at 15-year follow-up and (2) the imaging findings and outcomes for the high-tension group would be equivalent to the sex-, race-, age-, and activity level matched control group. Study Design:Randomized controlled trial; Level of evidence, 1. Methods:Consented patients underwent ACL reconstruction (ACLR) with bone-patellar tendon-bone or a 4-strand hamstring tendon autograft. A matched uninjured control group was assembled for comparison. Two laxity-based tensioning procedures were randomized: (1) tension set to restore normal anteroposterior (AP) laxity at time of surgery relative to the contralateral uninjured knee (low-tension group) or (2) tension set to overconstrain AP laxity at time of surgery relative to the contralateral knee (high-tension group). Baseline outcome measures, radiographs, and magnetic resonance imaging (MRI) scans were collected prior to surgery and at 15 years postoperatively. Results:For medial joint space width, the differences between limbs across the 3 groups were not significant. Within the tension groups, the Whole Organ MRI Score was significantly higher in the surgical knee relative to the contralateral knee in both groups, while the Osteoarthritis Research Society International radiographic scores were higher in the surgical knee in the low-tension group only. A total of 43% of patients in both tension groups met the Knee injury and Osteoarthritis Outcome Score composite criteria for a symptomatic knee compared with controls (10%; P = .01). Most other outcomes, including AP laxity, International Knee Documentation Committee knee examination score, and single-leg hop test were not significantly different between the 3 groups. Conclusion:The results do not support the hypotheses that patients in the high-tension group would have better chondroprotection compared with the low-tension group and have equivalent outcomes with the matched controls. Overall, the results show that patients undergoing ACLR are more likely to develop PTOA and display inferior outcomes compared with the uninjured matched control group, regardless of graft tension.

BACKGROUND:Anterior cruciate ligament (ACL) reconstruction (ACLR) in the presence of excessive posterior tibial slope (PTS) is a well-established risk factor for increased ACL graft forces and a heightened risk of graft failure. PURPOSE/HYPOTHESIS:The primary aim of this study was to evaluate whether lateral extra-articular tenodesis (LET) could mitigate the adverse effects of increased PTS on knee kinematics and ACL graft forces, achieving results comparable to those of slope-reducing osteotomy (SRO). It was hypothesized that LET would provide similar improvements in knee stability and graft force reduction to SRO in the presence of increased PTS. A secondary aim was to determine if an ALC injury exacerbates the effect of increased PTS on ACL graft forces and overall knee stability. It was hypothesized that ALC injury would amplify the negative effects of increased PTS. STUDY DESIGN:Controlled laboratory study. METHODS:Eight fresh-frozen cadaveric specimens were prepared, excluding those with previous surgery or significant knee pathology. ACLR was performed using a quadrupled hamstring tendon autograft. The effects of LET and SRO were tested at various degrees of PTS (0°, 10°, and 20°). A simulated pivot-shift maneuver was used to measure ACL graft loads, anterior tibial translation (ATT), and internal rotation (IR). Mixed-effects models were utilized to analyze the data. RESULTS:Increasing PTS resulted in significant increases in ACL graft forces (P < .001), ATT (P < .001), and IR (P < .001). LET reduced ACL graft loads by 22.1% at 10° and 36.6% at 20° of PTS. In contrast, a 10° SRO showed only a 2.6% reduction at 10° and 23.9% at 20° of PTS. There were no significant differences in graft forces between the postosteotomy states and LET augmentation states at both 10° and 20° of tibial slope, suggesting equivalent efficacy in reducing graft loads. Additionally, LET significantly decreased graft forces compared with the ALC-sectioned state (P = .019). Finally, ALC sectioning did not significantly increase ACL graft load compared with the ACLR-only condition (P = .320), nor did it exacerbate the effects of increased PTS on ATT and IR. CONCLUSION:LET effectively reduces ACL graft forces and improves knee stability in the presence of increased PTS, performing comparably to or better than SRO under simulated pivot-shift conditions. CLINICAL RELEVANCE:These findings suggest that LET is a viable alternative to SRO, particularly for patients with high PTS undergoing ACLR.

Recently, scientists have utilized a range of techniques in the attempt to model ligamentous structures, which play a vital role in the functioning of the human body. Therefore, our objective is to conduct a systematic scoping review that evaluates the scope of 163 journals pertaining to computational modeling of ligaments, while also assessing the limitations associated with each method. These limitations encompass various aspects, including anatomical considerations, subject specificity, viscoelasticity, mechanical properties, model-specific factors, and limitations related to medical imaging. The guiding question for this review is: What are the existing limitations in the surveyed literature regarding ligament modeling and methods, specifically with regard to time variance and environmental hazards? A search of PubMed/MEDLINE, Web of Science (WoS), and ScienceDirect was conducted following the scoping review methodology recommended by the Joanna Briggs Institute (JBI) for evidence-based healthcare. After applying the inclusion and exclusion criteria, 74 full-text articles were analyzed, revealing that each method possesses its own set of limitations and may not comprehensively encompass all aspects of ligament properties. Nevertheless, despite these limitations, the majority of these methods exhibit the ability to produce reliable outcomes.

Magnetic resonance imaging (MRI) has the potential to identify post-operative risk factors for re-tearing an anterior cruciate ligament (ACL) using a combination of imaging signal intensity (SI) and cross-sectional area measurements of the healing ACL. During surgery micro-debris can result from drilling the osseous tunnels for graft and/or suture insertion. The debris presents a limitation when using post-surgical MRI to assess reinjury risk as it causes rapid magnetic field variations during acquisition, leading to signal loss within a voxel. The present study demonstrates how K-means clustering can refine an automatic segmentation algorithm to remove the lost signal intensity values induced by the artifacts in the image. MRI data were obtained from 82 patients enrolled in three prospective clinical trials of ACL surgery. Constructive Interference in Steady State MRIs were collected at 6 months post-operation. Manual segmentation of the ACL with metallic artifacts removed served as the gold standard. The accuracy of the automatic ACL segmentations was compared using Dice coefficient, sensitivity, and precision. The performance of the automatic segmentation was comparable to manual segmentation (Dice coefficient = .81, precision = .81, sensitivity = .82). The normalized average signal intensity was calculated as 1.06 (±0.25) for the automatic and 1.04 (±0.23) for the manual segmentation, yielding a difference of 2%. These metrics emphasize the automatic segmentation model’s ability to precisely capture ACL signal intensity while excluding artifact regions. The automatic artifact segmentation model described here could enhance qMRI’s clinical utility by allowing for more accurate and time-efficient segmentations of the ACL.

BACKGROUND:Posttraumatic osteoarthritis (PTOA) arises secondarily to joint trauma and is driven by catabolic inflammatory pathways. Alpha-2-macroglobulin (α2M) is a naturally occurring proteinase inhibitor found in human serum and synovial fluid that binds proteases as well as proinflammatory cytokines involved in the pathogenesis of PTOA. PURPOSE:(1) To investigate the therapeutic potential of intra-articular α2M injections during the acute stages of PTOA by inhibiting inflammatory pathways driven by the cytokines expressed by the synovium in a large preclinical Yucatan minipig model and (2) to determine if 3 intra-articular α2M injections have greater chondroprotective effects compared with 1 intra-articular injection. STUDY DESIGN:Controlled laboratory study. METHODS:A total of 48 Yucatan minipigs were randomized into 4 groups (n = 12 each): (1) modified intra-articular drilling (mIAD) and saline (mIAD + saline), (2) mIAD and 1 intra-articular α2M injection (mIAD +α2M-1), (3) mIAD and 3 α2M injections (mIAD +α2M-3), and (4) sham control. Surgical hindlimbs were harvested at 15 weeks after surgery. Cartilage degeneration, synovial changes, inflammatory gene expression, and matrix metalloproteinase levels were evaluated. Gait asymmetry was measured before and after surgery using a pressure-sensing walkway system. RESULTS:Macroscopic lesion areas and microscopic cartilage degeneration scores were lower in the mIAD +α2M-1 and mIAD +α2M-3 groups compared with the mIAD + saline group (P < .05) and similar to those in the sham group (P > .05). Synovial membrane scores of the mIAD +α2M-1 and mIAD +α2M-3 groups were lower than that of the mIAD + saline group (P < .05) and higher than that of the sham group (P < .05). Interleukin-1 beta, nuclear factor kappa B, and tumor necrosis factor alpha mRNA expression in the synovium and matrix metalloproteinase-1 levels in synovial fluid were significantly lower in the mIAD +α2M-1 and mIAD +α2M-3 groups compared with the mIAD + saline group (P < .05). No significant differences were observed between the mIAD +α2M-1 and mIAD +α2M-3 groups for all measured outcomes. There were early changes in gait (P < .05) between preoperative and postoperative time points for the mIAD + saline, mIAD +α2M-1, and mIAD +α2M-3 groups that normalized by 15 weeks. CONCLUSION:Animals receiving early α2M treatment exhibited less cartilage damage, milder synovitis, and lower inflammation compared with animals with no α2M treatment. These results exemplify the early anti-inflammatory effects of α2M and provide evidence that intra-articular α2M injections may slow the progression of PTOA. CLINICAL RELEVANCE:In patients presenting with an acute joint injury, an early intervention with α2M may have the potential to reduce cartilage degeneration from catabolic pathways and delay the development of PTOA.

Objectives: There is growing recognition of the adverse impact of excess posterior tibial slope (PTS) on anterior cruciate ligament (ACL) graft forces, contributing to an increased failure rate in patients with excessive PTS. In patients with elevated PTS and a history of ACLR failure, a slope-reducing osteotomy has been offered as a surgical option. Lateral extra-articular tenodesis (LET) has also been proposed to augment knee stability, thereby diminishing ACL graft forces in patients burdened with excess PTS. Therefore, the primary aim of this biomechanical study was to evaluate whether LET could counteract the effects of excess PTS on knee kinematics and ACLR graft forces, to an extent akin to a slope-reducing osteotomy. Methods: Anatomic single-bundle ACL reconstruction (ACLR) was performed on seven fresh-frozen cadaveric specimens. To facilitate desired adjustments to the PTS, a posterior osteotomy was created, with direct measurements allowing for PTS’s of 0°, 10°, and 20°, as confirmed via lateral standard X-ray. Subsequent to ACLR, baseline biomechanical testing was conducted utilizing a six-degrees-of-freedom robot, outfitted with a custom load cell affixed to the ACL. Testing encompassed three sequential specimen states: ACLR only, ACLR with sectioning of the ALC, and finally, the incorporation of ACLR + LET. Assessments of anterior tibial translation (ATT), internal rotation (IR), and ACL graft forces were performed across the specified tibial slopes for each successive specimen state, following a simulated pivot shift maneuver (comprising 100 N compression, 10 Nm valgus torque, 5 Nm IR rotation torque). Within the ALC-sectioned state, the sectioning involved both the Anterolateral Ligament and Kaplan fibers at their respective attachment sites, while the LET state was attained via the modified Lemaire technique. The statistical methodology employed mixed models, incorporating classical sandwich estimation, with the application of Holm’s test for multiple comparisons. A p-value threshold of <0.05 was established as the criterion for statistical significance Results: At 10 degrees of PTS, LET reduced graft forces during pivot shift loading more than the 10-degree slope-reducing osteotomy (104.9 N vs 125.7 N, p=0.03). However, at 20 degrees of PTS, no statistically significant differences in graft loads were found between LET and 10-degree slope-reducing osteotomy (109.5 N vs 111.3 N, p=0.71) (Figure 1). Analysis of tibiofemoral kinematics revealed an inverse linear relationship between knee stability and increasing posterior tibial slope (PTS) (Figures 2 &3). Additionally, our data demonstrated that ALC sectioning potentiates the negative ramifications of excess posterior tibial slope on knee stability, and such stability was restored following LET at all degrees of tibial slope (p<0.001). In evaluating LET vs. 10-degree slope-reducing osteotomy, no significant differences in ATT (2.50 vs. 1.73 p=0.25; 2.70 vs. 3.25, p=0.25) and IR (23.93 vs. 21.91 p=0.17; 25.40 vs. 27.03 p=0.23) were noted. Conclusions: Excess PTS significantly increases anterolateral knee instability and ACL graft forces under pivot shift loading. At 10° PTS, LET outperformed a 10° slope-reducing osteotomy in reducing ACL graft forces but not at 20° PTS. Though less effective than osteotomy in graft force reduction at 20° PTS, LET matched osteotomy in improving knee stability, decreasing IR and ATT at both 10° and 20° PTS.

Background:Bridge-enhanced anterior cruciate ligament restoration (BEAR) combines suture repair of the anterior cruciate ligament (ACL) with an extracellular matrix implant plus autologous blood to facilitate native ACL healing. Purpose/Hypothesis:The purpose of this study was to compare the 6-year follow-up outcomes of patients who underwent the BEAR procedure with those of a nonrandomized concurrent control group receiving autograft ACL reconstruction (ACLR) in the first-in-human safety study of the BEAR implant (BEAR I trial). Based on the 2-year results, it was hypothesized that isometric hamstring strength after the BEAR procedure would be greater than that after ACLR and that there would be no other differences in outcomes at 6 years. Study Design:Cohort study, Level of evidence, 2. Methods:Ten patients underwent BEAR and 10 received ACLR with a 4-stranded hamstring autograft. Outcomes assessed included the record of subsequent surgeries, the International Knee Documentation Committee (IKDC) Subjective Knee Score, IKDC physical examination grade, the Knee injury and Osteoarthritis Outcome Score, instrumented knee laxity, functional outcomes (ie, muscle strength assessments and hop testing), and qualitative magnetic resonance imaging assessment. Comparisons between treatments were based on computations of the mean differences and the associated 95% CIs. Results:One patient in the BEAR group and 3 patients in the ACLR group were lost to follow-up. In the period between 2 and 6 years, 1 patient in each group underwent revision surgery. There were no differences between groups at the 6-year follow-up in any of the outcome measures except for isometric hamstring strength, which was approximately equal to that of the contralateral knee in the BEAR group and <44% of that in the contralateral knee in the ACLR group (P < .01). Conclusion:This preliminary study suggests that the outcomes of BEAR and ACLR with a hamstring tendon graft may be similar at the 6-year follow-up and warrants investigation of the BEAR procedure in a larger cohort of patients.

Objectives: Even young patients without prior injury to the knee develop radiographic changes during the first two years after anterior cruciate ligament reconstruction (ACLR), but it’s unknown whether these early changes are predictive of increased pain over the next several years. The purpose of this study is to determine whether radiographic changes at 2 years are predictive of increased pain at 6 years while controlling for factors known to be predictive of worse pain after ACLR. We hypothesized that worse radiographic changes would not be predictive of increased pain. Methods: Patients were part of a nested cohort who underwent ACLR for an athletic injury, had no prior injury to their knee, and were 35 years of age or younger at 2-year follow-up. These patients underwent standardized posteroanterior semi-flexed knee radiographs using the metatarsophalangeal (MTP) positioning technique at 2 years and completed questionnaires at baseline (at time of enrollment, just prior to their ACL surgery), 2 years, and 6 years. These questionnaires included demographic questions, the SF-36, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Marx Activity Level Scale. Surgeons completed an intraoperative data form that included physical examination and arthroscopy findings and treatments administered to the knee. Radiographs were graded by 2 graders using the semiquantitative atlas-based Osteoarthritis Research Society International (OARSI) scoring system, where scores of 0-3 are assigned in the medial and lateral compartments for features including osteophytes, joint space narrowing, sclerosis, and bony attrition. A directed acyclic graph (DAG) was used to plan the statistical models to assess the direct effect of radiographic change on pain at 6 years. A model was built using proportional odds logistic regression, and missing data were imputed using multivariate imputation via chained equation (MICE) for 20 cycles. The model controlled for baseline pain, age, sex, body mass index, years of education, baseline Marx, baseline SF-36, medial and lateral meniscus treatment, presence of cartilage lesion(s), allograft use, and incidence of subsequent surgery before 2 years. Results: A total of 421 subjects were included in the analysis cohort. The median age was 18 years at the time of enrollment (interquartile range [IQR]16-21 years), and 216 (51.3%) were female. 297 subjects (70.5%) had a normal medial meniscus, 85 (20.2%) had a repair, and 39 (9.3%) had a partial meniscectomy. A total of 257 subjects (61.0%) had a normal lateral meniscus, 30 (7.1%) had a repair, and 134 (31.8%) had a partial meniscectomy. 107 subjects (25.4%) had at least 1 Outerbridge grade 2 or worse cartilage lesion. Fifty-three subjects (12.6%) had subsequent surgery prior to their 2-year follow-up. The median total radiographic score on the 2-year radiographs was 4 (IQR 2.0-5.5) and ranged from 0 to 12.5. Median KOOS pain (where 100 = no pain) was 75 (IQR 63.9 to 86.1) at baseline, 96.9 (IQR 91.7 to 100) at 2 years, and 97.2 (IQR 88.9 to 100) at 6 years. Marx activity level (where 16 points = highest activity level) at baseline was 16 (IQR 12 to 16). After controlling for the other variables in the model, subjects with a total radiographic score of 5.5 had 6% increased odds of having increased KOOS pain at 6 years compared to patients with a total radiographic score 2, but this effect was not statistically significant (odds ratio = 1.06, 95% CI, 0.79-1.42, p = .698). Greater baseline pain (odds ratio 1.41, 95% CI 1.06-1.86, p = .018) and subsequent surgery prior to 2 years (odds ratio 0.52, 95% CI, 0.3-0.93, p = .026) were both statistically significant predictors of worse pain at 6-year follow-up. Conclusions: Even young, active patients begin to develop radiographic changes by 2 years after ACLR; however, these changes are not associated with increased pain up to 6 years postoperatively. This information is important for counseling patients who may be concerned about radiographic changes that are seen on x-rays obtained during the first few years after ACLR. In addition, this study suggests that treatment decisions around the time of surgery that can minimize baseline pain and decrease the incidence of subsequent surgery may improve patient pain levels at 6 years postoperatively.

Purpose (the aim of the study): Even young patients without prior injury to the knee develop radiographic changes during the first two years after anterior cruciate ligament reconstruction (ACLR), but it's unknown whether these early changes are predictive of increased pain over the next several years. The purpose of this study is to determine whether radiographic changes at 2 years are predictive of increased pain at 6 years while controlling for factors known to be predictive of worse pain after ACLR. We hypothesized that worse radiographic changes would not be predictive of increased pain.

Anterior cruciate ligament (ACL) injury, particularly in increasingly young and active adolescents, continues to pose a clinical challenge with re-injury rates reported as high as 30%. Evidence also suggests that current standard-of-care ACL reconstruction (ACLR) does not mitigate post-traumatic osteoarthritis (PTOA) risk. Bridge- enhanced ACL restoration (BEAR) is a recently developed and tested ACL surgery that promotes primary healing of the native ACL with excellent early results. BEAR has shown to reduce signs of early PTOA compared to ACLR in an animal model. Here, we describe a theoretical framework related to re-innervation that can clarify why the outcomes of ACLR and BEAR surgeries differ. We also discuss how ongoing and new challenges in determining return-to-sport readiness following the competing surgeries may differ, and how emerging imaging tools and measures of neuromuscular function may aid in clinical decision-making to decrease the likelihood of re-injury and PTOA risk.

Normalized signal intensity (SI) obtained from magnetic resonance imaging (MRI) has been used to track anterior cruciate ligament (ACL) postoperative remodeling. We aimed to assess the effect of MRI sequence (PD: proton density-weighted; T2: T2-weighted; CISS: constructive interference in steady state) on postoperative changes in healing ACLs/grafts. We hypothesized that CISS is better at detecting longitudinal SI and texture changes of the healing ACL/graft compared to the common clinical sequences (PD and T2). MR images of patients who underwent ACL surgery were evaluated and separated into groups based on surgical procedure (Bridge-Enhanced ACL Repair (BEAR; n = 50) versus ACL reconstruction (ACLR; n = 24)). CISS images showed decreasing SI across all timepoints in both the BEAR and ACLR groups (p < 0.01), PD and T2 images showed decreasing SI in the 6-to-12- and 12-to-24-month postoperative timeframes in the BEAR group (p < 0.02), and PD images additionally showed decreasing SI between 6- and 24-months postoperation in the ACLR group (p = 0.02). CISS images showed texture changes in both the BEAR and ACLR groups, showing increases in energy and decreases in entropy in the 6-to-12- and 6-to-24-month postoperative timeframes in the BEAR group (p < $\lt $ 0.04), and increases in energy, decreases in entropy, and increases in homogeneity between 6 and 24 months postoperation in the ACLR group (p < 0.04). PD images showed increases in energy and decreases in entropy between 6- and 24-months postoperation in the ACLR group (p < 0.008). Finally, CISS was estimated to require a smaller sample size than PD and T2 to detect SI differences related to postoperative remodeling.

To determine the transcriptomic changes seen in early- to mid-stage posttraumatic osteoarthritis (PTOA) development, 72 Yucatan minipigs underwent transection of the anterior cruciate ligament. Subjects were randomized to no further intervention, ligament reconstruction, or ligament repair, followed by articular cartilage harvesting and RNA-sequencing at three different postoperative timepoints (1, 4, and 52 weeks). Six additional subjects received no ligament transection and provided cartilage tissue to serve as controls. Differential gene expression analysis between post-transection cartilage and healthy cartilage revealed an initial increase in transcriptomic differences at 1 and 4 weeks followed by a stark reduction in transcriptomic differences at 52 weeks. This analysis also showed how different treatments genetically modulate the course of PTOA following ligament disruption. Specific genes (e.g., MMP1, POSTN, IGF1, PTGFR, HK1) were identified as being upregulated in the cartilage of injured subjects across all timepoints regardless of treatment. At the 52-week timepoint, 4 genes (e.g., A4GALT, EFS, NPTXR, ABCA3) that-as far as we know-have yet to be associated with PTOA were identified as being concordantly differentially expressed across all treatment groups when compared to controls. Functional pathway analysis of injured subject cartilage compared to control cartilage revealed overarching patterns of cellular proliferation at 1 week, angiogenesis, ECM interaction, focal adhesion, and cellular migration at 4 weeks, and calcium signaling, immune system activation, GABA signaling, and HIF-1 signaling at 52 weeks.

Neuromuscular function is thought to contribute to posttraumatic osteoarthritis (PTOA) risk in anterior cruciate ligament (ACL)-reconstructed (ACLR) patients, but sensitive and easy-to-use tools are needed to discern whether complex muscle activation strategies are beneficial or maladaptive. Using an electromyography (EMG) signal analysis technique coupled with a machine learning approach, we sought to: (1) identify whether ACLR muscle activity patterns differed from those of healthy controls, and (2) explore which combination of patient outcome measures (thigh muscle girth, knee laxity, hop distance, and activity level) predicted the extent of osteoarthritic changes via magnetic resonance imaging (MRI) in ACLR patients. Eleven ACLR patients 10-15 years post-surgery and 12 healthy controls performed a hop activity while lower limb muscle EMG was recorded bilaterally. Osteoarthritis was evaluated based on MRI. ACLR muscle activity patterns were bilaterally symmetrical and differed from those of healthy controls, suggesting the presence of a global adaptation strategy. Smaller ipsilateral thigh muscle girth was the strongest predictor of inferior MRI scores. The ability of our EMG analysis approach to detect meaningful neuromuscular differences that could ultimately be related to thigh muscle girth provides the foundation to further investigate a direct link between muscle activation patterns and PTOA risk.

Purpose: Alterations in gene expression of articular cartilage and synovium are one of the first detectable markers of post-traumatic osteoarthritis (PTOA) following injury. However, little is known about the gene expression relationship between these two tissues several months into disease progression. The purpose of this study was to gauge the extent to which anterior cruciate ligament (ACL) transection induces different transcriptomic changes in synovium compared to articular cartilage 52 weeks following injury.